Role of RASGRF1 in Neurofibromatosis - Validating a Potential Therapeutic Target
Final rept. 1 Jun 2002-31 Mar 2006
CORNELL UNIV ITHACA NY
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It was hypothesized that the gene encoding the RASGRF1 protein, a GTP exchange factor GEF, controls the severity of neurofibromatosis. Over-expression of the Rasgrf1 gene was predicted to exacerbate neurofibromatosis while Rasgrf1 silencing will attenuate it. Two novel strains of mice ideally suited to test this hypothesis that were developed in my lab were used to evaluate the role or RASGRF1 on the manisfestations of neurofibromatosis type 1. One strain of mice over-express Rasgrf1, the other has diminished expression. These were crossed with a mouse model for NF1 and the effects of the altered level of RASGRF1 protein on tumorigenesis were monitored. The results of these studies support the hypothesis that attenuating the GEF activity of RASGRF1 protein also attenuates tumorigenic pathways controlled by NF1. Also, in characterizing the strains of mice we developed for this study, we obtained new insights into the regulation and functions of the Rasgrf1 gene.
- Medicine and Medical Research